综合分析夏枯草在甲状腺癌转移中的作用机制

IF 6.7 1区 医学 Q1 CHEMISTRY, MEDICINAL
Shifan Zeng , Benjuan Liu , Rui Ge , Zhilong Yuan , Yunyun Yang , Weiqiang Zhu , Zhuo Wang
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引用次数: 0

摘要

背景:甲状腺乳头状癌(PTC)的淋巴结转移(LNM)是导致预后不良的主要因素。传统中草药Prunella vulgaris (P. vulgaris)具有抑制PTC转移的潜力,但其分子机制尚不清楚。目的探讨凡草抗PTC转移作用的分子机制,重点鉴定关键活性化合物及其靶基因。方法采用srna测序技术鉴定PTC与LNM组织间的差异表达基因(DEGs)。从TCMSP和BATMAN-TCM中分离得到寻常草的活性化合物和靶点,并与DEGs结合构建化合物-靶点网络。应用机器学习算法鉴定与β-谷甾醇(BS)相关的枢纽基因。体外检测BS和ADRB2对细胞活力、增殖、迁移、侵袭、线粒体膜电位(MMP)和活性氧(ROS)的影响。结果共鉴定出696个DEGs和195个P. vulgaris靶点,其中有91个重叠基因与DEGs和P. vulgaris靶点相交。在这个网络中,17个目标基因与BS相关,五种机器学习算法一致将ADRB2确定为中心枢纽。ADRB2在LNM组织中表达显著升高,与临床病理特征密切相关。BS治疗可抑制PTC细胞生长和转移相关行为,并可通过ADRB2过表达逆转。结论bs是PTC的活性成分,通过靶向ADRB2,诱导线粒体功能障碍,抑制PTC转移的关键过程。这些发现不仅首次提供了将BS与adrb2介导的PTC抗转移活性联系起来的实验证据,而且为从传统草药中鉴定治疗性化合物提供了一种新的综合方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

An integrative analysis reveals mechanisms of Prunella vulgaris in thyroid cancer metastasis

An integrative analysis reveals mechanisms of Prunella vulgaris in thyroid cancer metastasis

Background

Lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC) is a major contributor to poor prognosis. Prunella vulgaris (P. vulgaris), a traditional medicinal herb, has shown potential in inhibiting PTC metastasis, but its molecular mechanism remains unclear.

Objectives

This study aimed to elucidate the molecular mechanisms by which P. vulgaris exerts its anti-metastatic effects on PTC, focusing on identifying key active compounds and their target genes.

Methods

RNA sequencing was used to identify differentially expressed genes (DEGs) between PTC and LNM tissues. Active compounds and targets of P. vulgaris were obtained from TCMSP and BATMAN-TCM and integrated with DEGs to construct a compound-target network. Machine-learning algorithms were applied to identify hub genes related to β-sitosterol (BS). The effects of BS and ADRB2 on cell viability, proliferation, migration, invasion, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) were examined in vitro.

Results

696 DEGs and 195 P vulgaris targets were identified, with 91 overlapping genes intersecting DEGs and P. vulgaris targets. Within this network, 17 target genes were associated with BS, and five machine-learning algorithms consistently identified ADRB2 as a central hub. ADRB2 expression was significantly elevated in LNM tissues and closely correlated with clinicopathological features. BS treatment inhibited PTC cell growth and metastasis-related behaviors, which were reversed by ADRB2 overexpression.

Conclusion

BS, an active component of P. vulgaris, inhibits key processes associated with PTC metastasis by targeting ADRB2 and inducing mitochondrial dysfunction. These findings not only provide the first experimental evidence linking BS to ADRB2-mediated anti-metastatic activity in PTC, but also offer a novel integrated approach for identifying therapeutic compounds from traditional herbs.
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来源期刊
Phytomedicine
Phytomedicine 医学-药学
CiteScore
10.30
自引率
5.10%
发文量
670
审稿时长
91 days
期刊介绍: Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.
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